Objective: Our research objectives were to evaluate the extent to which cognitive and physical performance in older adults, when fresh, and when fatigued vary with age and habitual physical activity. Methods: We employed experimental study designs, with between- (Study 1: age: 51–64 and 65–80 years and Study 2: habitual physical activity: active and sedentary) and within-participants factors (Study 1: test: before cognitive task and after cognitive task and Study 2: session: fatigue and control and test: before and after cognitive task). In testing sessions, participants performed exercise (6-min walk, 30-s sit stand, and 30-s arm curl) and cognitive (response inhibition and vigilance) tasks before and after a 20-min demanding cognitive task (time load dual back [TLDB] task). In Study 2, participants completed a paced breathing task (control session) as well as the TLDB (fatigue session). Ratings of mental fatigue and exercise-related perceived exertion were obtained. Results: The 20-min TLDB task elicited a state of mental fatigue. Cognitive and physical performance was worse after than before the TLDB task. These impairments in performance were moderated by age (Study 1) and habitual physical activity (Study 2). Conclusion: The deleterious effects of mental fatigue on cognitive and physical performance were accentuated by aging and attenuated by habitual physical activity. Implications: Cognitive and/or physical training could mitigate the negative effects of mental fatigue on performance in older adults.